FOCMA is a transformation or tumor-specific antigen induced by the RNA-containing leukemia and sarcoma viruses of cats. In experimental and field conditions FOCMA is the target for an efficient anti-tumor immune surveillance mechanism which prevents the appearance of spontaneous lymphoid malignancies. We plan to characterize the immune mechanisms which prevent appearance of cat leukemias. The major assay system used will be the 51Cr release cytotoxicity assay and emphasis will be placed on using assay mixtures which contain only cat components. We will study the activity of all known immunological effector mechanisms and attempt to piece together the interactions between them. As such we will assay for naturally occurring mechanisms, i.e., N.K. cells and the virolytic effect of complement, as well as immune mechanisms, i.e., cellular cytotoxicity mediated by T cells and/or macrophages, antibody-dependent cellular cytotoxicity and ADCC effector cell levels, virus-neutralizing antibody, complement-dependent antibody and complement levels. The nature and magnitude of these responses in cats will be defined before and after natural exposure (or inoculation with leukemia or sarcoma virus), and changes following the onset of persistent viremia or appearance of tumors will be investigated. In parallel studies we will investigate the quantitative expression and cross-reactivity of FOCMA on individual tumor isolates.